Primary Tumor Resection With Sintilimab and Chemotherapy in Advanced NSCLC

NCT07177105 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ES-2025-159-02
• Study Type: interventional
• Target: 118
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to evaluate whether resecting the primary tumor can improve the outcomes of treatment with sintilimab and chemotherapy in advanced EGFR/ALK-negative non-small cell lung cancer (NSCLC). Patients will be randomly assigned to one of two groups: one group will undergo primary tumor resection followed by sintilimab, pemetrexed, and carboplatin, while the other group will only receive sintilimab, pemetrexed, and carboplatin. The study will assess progression-free survival, overall survival, treatment response, safety, and the impact of treatment on quality of life. Through this study, we hope to determine whether primary tumor resection can provide additional benefits of anti-PD-1 therapy and chemotherapy for advanced NSCLC.

Conditions

Non Small Cell Lung Cancer

Keywords

Sintilimab; Chemotherapy; Surgery; Advanced NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from randomization to the first documentation of disease progression (PD) or death from any cause, whichever occurs first. Disease progression will be assessed by the Independent Radiology Review Committee (IRRC) according to RECIST version 1.1 criteria.

  From randomization until the first documentation of disease progression or death from any cause, whichever occurs first (up to 5 years).

Secondary Outcomes (6)

• Overall Survival (OS)

  Randomization to death from any cause (up to 5 years).

• Objective Response Rate (ORR)

  Randomization until disease progression or death, which ever occurs first (up to 5 years).

• Disease Control Rate (DCR)

  Randomization until disease progression or death, which ever occurs first (up to 5 years).

• Adverse Events

  Randomization up to approximately 5 years.

• Quality of Life (QoL) evaluated by European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30)

  Randomization until disease progression or death, which ever occurs first (up to 5 years).

Study Arms (2)

Surgery

ACTIVE COMPARATOR

Participants will first undergo cytoreductive surgery. After adequate postoperative recovery within 2-4 weeks, they will receive therapy consisting of intravenous administration of sintilimab, pemetrexed, and carboplatin on Day 1 of each 3-week cycle, for a total of 4 cycles. During the maintenance phase, participants will receive sintilimab and pemetrexed until the duration of sintilimab treatment reaches 31 cycles, or the total treatment duration from randomization reaches 2 years, or until disease progression or the occurrence of unacceptable toxicity.

Drug: Immunochemotherapy

Intervention Group

EXPERIMENTAL

Participants will receive induction therapy consisting of intravenous administration of sintilimab, pemetrexed, and carboplatin on Day 1 of each 3-week cycle, for a total of 4 cycles. During the maintenance phase, participants will receive sintilimab and pemetrexed until the duration of sintilimab treatment reaches 31 cycles, or the total treatment duration from randomization reaches 2 years, or until disease progression or the occurrence of unacceptable toxicity.

Procedure: Cytoreductive surgery; Drug: Immunochemotherapy

Interventions

Cytoreductive surgery PROCEDURE

* Preoperative evaluation must confirm resectability. Thoracoscopic minimally invasive surgery will be performed, with the surgical approach selected according to disease conditions, such as lobectomy, segmentectomy, wedge resection, or sleeve resection; ② Systematic mediastinal lymph node dissection or lymph node sampling (based on preoperative imaging and intraoperative evaluation) must be performed; ③ Postoperative recovery must be adequate (postoperative complications ≤ Clavien-Dindo grade II).

Intervention Group

Immunochemotherapy DRUG

1. Treatment phase: ① Sintilimab Dose: 200 mg, administered intravenously over 30 minutes or less; ② Pemetrexed Dose: 500 mg/m², administered intravenously over 10 minutes or less; ③ Carboplatin Dose: administered according to the area under the curve (AUC) of 5 mg/mL/min, with infusion time controlled within 15-60 minutes. The above regimen will be administered every 3 weeks after surgery for a total of 4 cycles. 2. Maintenance phase: * Sintilimab Dose: 200 mg, administered intravenously over 30 minutes or less; ② Pemetrexed Dose: 500 mg/m², administered intravenously over 10 minutes or less; The above regimen will be administered every 3 weeks. Maintenance with sintilimab will continue for up to 31 cycles, or the total duration of systemic therapy from randomization will not exceed 2 years, or until disease progression or the occurrence of unacceptable toxicity

Intervention Group; Surgery

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years, no sex limitation;
• Histologically or cytologically confirmed stage III-IV non-squamous NSCLC, deemed unresectable (evaluated by MDT);
• Negative for EGFR mutation and ALK rearrangement (tested by ARMS-PCR, NGS, or equivalent methods);
• No histological evidence of small cell lung cancer (SCLC) or transformation to SCLC;
• No prior exposure to anti-tumor therapy;
• ECOG performance status of 0-1;
• Expected survival ≥ 6 months;
• Primary tumor diameter ≥ 1 cm, with at least one measurable lesion remaining after resection (per RECIST v1.1 criteria);
• Adequate major organ function, including:
• ① Hematologic: absolute neutrophil count ≥ 1.5 × 10⁹/L, platelets ≥ 100 × 10⁹/L, hemoglobin ≥ 9.0 g/dL;
• ② Hepatic: ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN in case of liver metastases), total bilirubin ≤ 1.5 × ULN;
• Renal: serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula);
• Pulmonary function (patients must meet at least one of the following to ensure adequate postoperative pulmonary reserve):
• ① FEV1 ≥ 1.2 L (or ≥ 40% of predicted value);
• ② FEV1/FVC ≥ 0.7, excluding severe obstructive ventilatory impairment;

You may not qualify if:

• Impaired immune function: history of primary immunodeficiency; history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active brain metastases. Patients with adequately treated brain metastases may be eligible if they have remained neurologically stable for at least 2 weeks prior to study entry and are not receiving systemic corticosteroids or are on a stable/reducing dose equivalent to ≤10 mg prednisone daily.
• Pregnancy.
• Presence of any severe, uncontrolled, or unstable comorbidity that, in the opinion of the investigator, may interfere with the patient's participation in the study or affect the interpretation of study results, including uncontrolled seizures, psychiatric disorders, active or uncontrolled infections, or other conditions (including laboratory abnormalities).

Sponsors & Collaborators

• Jianxing He: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cytoreduction Surgical Procedures

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Central Study Contacts

Jianxing He, Ph.D

CONTACT

86+020-83062807; drjianxing.he@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: The First Affiliated Hospital of Guangzhou Medical University

Study Record Dates

• First Submitted: September 6, 2025
• First Posted: September 16, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2030
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share